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| 2. |
- Bennet, Sean M. P., et al.
(författare)
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Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs
- 2018
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:5, s. 872-881
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Tidskriftsartikel (refereegranskat)abstract
- Objective The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response. Design Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available. Results Responders (reduced IBS-SSS by >= 50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption. Conclusions A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles.
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- Böhn, Lena, et al.
(författare)
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Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome as Well as Traditional Dietary Advice: A Randomized Controlled Trial.
- 2015
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 149:6
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Tidskriftsartikel (refereegranskat)abstract
- A diet with reduced content of fermentable short-chain carbohydrates (fermentable oligo-, di-, monosaccharides, and polyols [FODMAPs]) has been reported to be effective in the treatment of patients with irritable bowel syndrome (IBS). However, there is no evidence of its superiority to traditional dietary advice for these patients. We compared the effects of a diet low in FODMAPs with traditional dietary advice in a randomized controlled trial of patients with IBS.
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| 7. |
- Carlert, Sara, et al.
(författare)
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Evaluation of the use of Classical Nucleation Theory for predicting intestinal crystallization of two weakly basic BCS class II drugs
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this work was to evaluate an in vitro-in silico approach for prediction of small intestinal crystallization of two weakly basic model BCS class II drugs, AZD0865 and mebendazole, and the effect crystallization would have on the absorption prediction of the drug. The crystallization rates were investigated in an in vitro method using simulated gastric and intestinal media, and the result was modeled by using Classical Nucleation Theory (CNT). The effect of varying in vitro parameters (initial drug concentration, rate of mixing gastric and intestinal fluid, stirring and filtration) on the interfacial tension g, being a key parameter in CNT, was investigated. The initial drug concentration had the most significant effect on g for both substances tested, although g is a fundamental parameter independent of concentration according to CNT. In the subsequent in silico prediction of drug absorption an empirical approach was used where g was predicted at expected in vivo small intestinal concentrations. The results showed that lack of crystallization effects on absorption in man of the model drug AZD0865 up to doses of 4 mg/kg could be predicted. Mebendazole intestinal precipitation in canines was also well described by the model, where mean predicted amount precipitated was 111% (range 41-166%) of measured solid amount, and mean predicted supersaturation was 106% (range 73-118%) of measured supersaturation. The plasma concentration of mebendazole after duodenal administration of a solution could not be predicted by the model with the same precision in the absence of measured intestinal drug concentrations as basis for estimating the g value. In conclusion, the in vitro-in silico approach can be used for predictions of absorption effects of crystallization, but the model could benefit from further development work on the theoretical crystallization model and in vitro experimental design.
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| 8. |
- Carlert, Sara, et al.
(författare)
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In Vivo Dog Intestinal Precipitation of Mebendazole : A Basic BCS Class II Drug
- 2012
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 9:10, s. 2903-2911
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate in viva intestinal precipitation of a model drug mebendazole, a basic BCS class II drug, using dogs with intestinal stomas for administration or sampling. After oral administration of a solution with an expected intestinal supersaturation of approximately 20 times the solubility, the measured supersaturation in dog intestinal fluid (DIE) was up to 10 times and, on average, only 11% of the given dose was retrieved as solid drug in the collected fluid from the stoma. The drug was rapidly absorbed with >90% of the total systemic exposure reached within three hours after duodenal administration of a solution. In silico absorption modeling showed that in vivo data were reasonably well described by a nonprecipitating solution. An in vitro model of precipitation in DIF predicted that the intestinal concentration of dissolved mebendazole would be less than 1/5 of the initial concentration within 10 min at concentrations comparable to in vivo. It was concluded that intestinal precipitation did not have any major influence on mebendazole absorption. The extent of precipitation was overpredicted in vitro given the in vivo absorption rate, and further work is needed to identify in vitro factors that could enable more accurate in vivo predictions of intestinal precipitation from solutions.
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| 9. |
- Carlert, Sara, et al.
(författare)
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Predicting intestinal precipitation : a case example for a basic BCS class II drug
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:10, s. 2119-2130
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the prediction accuracy of in vitro and in vitro/in silico methods for in vivo intestinal precipitation of basic BCS class II drugs in humans. METHODS: Precipitation rate of a model drug substance, AZD0865 (pKa = 6.1; log K(D) = 4.2), was investigated in vitro using simulated intestinal media, and calculations of the crystallization rates were made with a theoretical model. Human intestinal precipitation was estimated by analysis of pharmacokinetic data from clinical studies at different doses. RESULTS: All in vitro models predicted rapid drug precipitation, where the intestinal concentration of dissolved AZD0865 at the highest dose tested was expected to decrease to half after less than 20 min. However, there was no indication of precipitation in vivo in humans as there was a dose proportional increase in drug plasma exposure. The theoretical model predicted no significant precipitation within the range of expected in vivo intestinal concentrations. CONCLUSIONS: This study indicated that simple in vitro methods of in vivo precipitation of orally administered bases overpredict the intestinal crystalline precipitation in vivo in humans. Hydrodynamic conditions were identified as one important factor that needs to be better addressed in future in vivo predictive methods.
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- Gröndahl, Hans-Göran, 1940, et al.
(författare)
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Titta på dina bitewingbilder-andra gör det inte!
- 2005
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Ingår i: Tandläkartidningen. ; 97:7, s. 60-66
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- De vanligaste röntgenbilder som tandläkare tar är utan tvivel bitewingbilder. Bitewingbilder kan också tas av en tandhygienist vid uppföljning av revisionspatienter. Bilder som tas av hygienister ska dock lämnas till en tandläkare för diagnostik av annat än karies och benförlust som orsakats av parodontit. Varje år tas flera miljoner bitewingbilder i Sverige. De har huvudsakligen två syften: 1) att vara till hjälp vid kariesdiagnostik och 2) för bedömning av det marginala benet. I den stora mängd bilder som tas dyker det då och då upp tecken på patologiska tillstånd av annan och ibland allvarligare art. Det är viktigt att vara medveten om den risken. Det ökar möjligheten att i ett tidigt stadium uppmärksamma sådana processer. Till en specialistklinik för odontologisk radiologi remitteras huvudsakligen patienter som kräver undersökningar som inte kan utföras i allmänpraktik. Hittar specialisterna en större patologisk process som troligen utvecklats under flera år letar de sig alltid bakåt i tiden. De gör det av två skäl: 1) det underlättar diagnostiken och 2) det ökar kunskaperna om på vilket sätt, och hur snabbt, olika typer av patologiska förändringar utvecklas. Tidigare tagna röntgenbilder och journalanteckningar kan berätta något om symtom eller kliniska tecken. När röntgenbilderna granskas kan specialisterna ibland se att det patologiska tillståndet funnits med i bilden men inte uppmärksammats. På följande sidor presenteras några sådana fall. Författarna spekulerar i varför upptäckterna inte gjordes tidigare och föreslår åtgärder som förhoppningsvis innebär att fler upptäckter kan göras i tidigare sjukdomsstadier. På så sätt kan behandlingen bli enklare och resultatet bättre.
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